Abstract: HIV entry inhibitors can effectively prevent HIV infection mainly by interfering with the fusion process of virus envelope and cell membrane. During the entry of HIV into cells, HIV-coated glycoprotein gp120 first binds with CD4 molecules on host cell membrane to cause conformational changes of gp120. Then, the subsequent binding of gp120 with CCR5 or CXCR5 induces conformational changes of gp41, making the virus further approach and finally fuse to target cell. Strategies like screening for compounds that bind to gp120, designing CD4 mimics, developing CD4 or CCR5 monoclonal antibodies and constructing accessory receptor inhibitors have been developed to prevent viral entry. The progresses in targets of HIV entry inhibitors and new drugs R & D have been reviewed in this paper.